This study proposes to explore the biochemical pathogenesis of renal dysfunction secondary to trace metal intoxication and magnesium depletion. The majority of studies will be performed on experimental animals (rats) chronically exposed to an excess of the trace metal or on a magnesium deficient diet. When renal tubular abnormalities appear, the kidneys will be removed and examined by electron microscopy, by emission spectroscopy (for trace metal analysis) and biochemically, focussing on alterations in ATP synthesis and Na-K-ATPase activity. The effect of Vitamin D on the renal tubular dysfunction and biochemical abnormalities will also be explored. Patients with acquired renal dysfunction secondary to industrial exposure from trace metals will also be studied in detail. The tubular abnormalities will be categorized and correlated with trace metal content of urine and hair. Attempts will be made to reverse the renal lesion by the use of chelating agents.